a study of onapristone er alone or in combination with anastrozole in gynecologic cancers that respond to progesterone

Conditions: Granulosa Cell Ovarian Cancer; Low Grade Serous Ovarian/ Primary Peritoneal Cancer; Endometrioid Endometrial Cancer

Summary: the purpose of this study is to test any good and bad effect of the study drug, onapristone extended-release (er) alone and in combination with anastrozole.


Eligibility criteria:
inclusion criteria: * histologically confirmed diagnosis at msk of either (1) granulosa cell ovarian cancer, (2) low grade serous ovarian/ primary peritoneal cancer, or (3) endometrioid endometrial cancer; with pr expression ≥1% by ihc on archival tissue taken within the prior 3 years or new biopsy if no archival tissue is available. ihc results do not have to be from msk. * measurable disease as defined by recist 1.1. measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension. each lesion must be ≥10mm when measured by ct or mri. lymph nodes must be ≥15mm in short axis when measured by ct or mri * patients must have had one prior chemotherapy regimen for management of disease. note: additional lines of chemotherapy, biologic or immunotherapy are allowed. * recovery from effects of recent surgery, radiotherapy, or chemotherapy * at least 4 weeks out from their last dose of radiation therapy * at least 4 weeks post-op from any major surgical procedure * at least 3 weeks out from their last dose of chemotherapy and/or biologic/targeted therapy * must be ≥ 18 years of age * karnofsky performance status (kps) of ≥ 70% * women of child-bearing potential must have a negative pregnancy test within 14 days prior to commencement of study treatment * women of child bearing potential must use an effective form of contraception during study and for at least 6 months after completion of study treatment * laboratory test findings performed within 14 days prior to initiation of study drug showing: * bone marrow function: * absolute neutrophil count (anc) ≥ 1,000/mcl * platelets ≥ 75,000/mcl * hemoglobin ≥ 8 g/dl * renal function: °creatinine ≤ 1.5 x uln * hepatic function: * bilirubin ≤ 1.5 x uln * ast and alt ≤ 2.5 x uln * resolution of all acute toxic effects of prior therapy to nci ctcae (version 5.0) grade ≤ 1, with the exception of unresolved grade 2 neuropathy and grade 2 alopecia, which are allowed * patient has recovered from any prior radiotherapy * patients must be able to swallow tablets whole, without crushing exclusion criteria: * history of another invasive malignancy (other than non-melanoma skin cancer or curatively treated in situ carcinoma) with evidence of disease within the past 3 years * history of prior hormonal therapy (i.e., megesterol acetate, tamoxifen or aromatase inhibitors) for treatment of cancer within 28 days before starting study drug * any psychological, familial, sociological or geographic condition that would potentially hamper compliance with the study protocol * known brain metastasis which have not been treated or showed stability for ≥ 6 months * patient has received an oral or iv corticosteroid within the prior 28 days and requires chronic corticosteroid therapy (excludes use of steroid premeds for ct allergy) * uncontrolled hypertension (systolic bp ≥ 160 mmhg or diastolic bp ≥ 95mmhg) despite medical treatment. patients with a history of hypertension are allowed provided blood pressure is controlled by anti-hypertensive treatment. * clinically significant heart disease as evidenced by myocardial infarction or arterial thrombotic event within the past 6 months, severe or unstable angina, or new york heart association (nyha) class ii-iv heart disease or cardiac ejection fraction measurement of \< 50% at baseline * refractory nausea and vomiting, requirement for parenteral hydration and/or nutrition, drainage gastrostomy tube, malabsorption, external biliary shunt, or significant small bowel resection that would preclude adequate study drug absorption * anticipated or ongoing administration of anti-cancer therapies other than those administered in this study * use of any prescription medication during the prior 28 days of first onapristone dosing that the investigator judges is likely to interfere with onapristone activity; specifically strong inhibitors or inducers, or sensitive substrates of cytochrome p450 cyp3a4. investigators should consult the following table of clinically-relevant products http://medicine.iupui.edu/clinpharm/ddis/clinical-table.

Keywords: onapristone er (apristor) oral progesterone progesterone receptor positive (pr+) anastrozole 19-061